OBJECTIVE To investigate negative contractile responses in the left ventricle during low-dose dobutamine (LDD) gated single-photon emission computed tomography (SPECT) in patients with ischemic cardiomyopathy. METHODS Sixty-eight consecutive patients (mean age, 60 + or - 11 years; 7 male) with ischemic cardiomyopathy (i.e., left ventricular ejection fraction [LVEF] < or = 40%) were evaluated using gated-SPECT at rest and during LDD infusion. Associations between a negative contractile reserve (i.e., a > or = 1-grade improvement in wall thickening score with LDD infusion) and scintigraphic viability criteria and coronary angiography findings were analyzed. RESULTS Some 42.6% (29/68) of patients had a negative contractile reserve in one or more segments. In 14.7% (n=10), the LVEF decreased by > or = 4% with LDD. These patients had more segments with a negative contractile reserve (2.8 + or - 2.5 vs. 0.87 + or - 0.40; P=.042), and the cut-off value on receiver operating characteristic curve analysis was > or =2 segments with a negative contractile reserve (sensitivity 70%, specificity 74%, positive likelihood ratio 2.71, negative likelihood ratio 0.40). Some 94% (74/79) of segments with a negative contractile reserve were in viable myocardium (i.e. normal or viable on scintigraphy). Twelve of 17 segments with akinesia or severe hypokinesia and a negative contractile reserve satisfied scintigraphic viability criteria, with the majority (10/12) lying in territories supplied by a patent coronary artery. CONCLUSIONS A negative contractile reserve was not uncommon in patients with ischemic cardiomyopathy and was associated with a general decrease in left ventricular systolic function. It was observed mainly in myocardial segments that appeared viable on scintigraphy and were supplied by a patent coronary artery.